Gomes F, Tahara EB, Busso C, Kowaltowski AJ, Barros MH

S. cerevisiae has three distinct inner mitochondrial membrane NADH dehydrogenases mediating the transfer of electrons from NADH to Coenzyme Q (CoQ): Nde1p, Nde2p and Ndi1p. The active site of Ndi1p faces the matrix side, while the enzymatic activities of Nde1p and Nde2p are restricted to the intermembrane space side, where ...

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they are responsible for cytosolic NADH oxidation. Here, we genetically manipulate yeast strains in order to alter the redox state of CoQ and NADH dehydrogenases to evaluate the consequences on mtDNA maintenance. Interestingly, nde1 deletion was protective for mtDNA in strains defective in CoQ function. Additionally, the absence of functional Nde1p promoted a decrement in the rate of hydrogen peroxide (H2O2) release in isolated mitochondria from different yeast strains. On the other hand, over-expression of the predominant NADH-dehydrogenase NDE1 elevated the rate of mtDNA loss and was toxic to coq10 and coq4 mutants. Increased CoQ synthesis through COQ8 over-expression also demonstrated that there is a correlation between CoQ respiratory function and mtDNA loss: supra-physiological CoQ levels were protective against mtDNA loss in the presence of oxidative imbalance generated by Nde1p excess or exogenous H2O2. Altogether, our results indicate that impairment in the oxidation of cytosolic NADH by Nde1p is deleterious toward mitochondrial biogenesis due to an increment in reactive oxygen species release.

Date: Nov. 02, 2012

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